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Completed

NCT Number: NCT05233033

Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients with Relapsed or Refractory B-cell NHL

This Phase 1a/1b study will evaluate the safety, tolerability and the pharmacokinetics/ pharmacodynamics (PK/ PD) of KT-413 in patients with R/R NHL. The Phase 1a stage of the study will explore escalating doses of single-agent KT-413. The Phase 1b stage will be split into 2 expansion cohorts to further characterize the safety, tolerability and the pharmacokinetics/ pharmacodynamics (PK/ PD) of KT-413 in MYD88 mutant and MYD88 wild-type R/R DLBCL.

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Key information

Conditions

Non Hodgkin Lymphoma DLBCL Diffuse Large B Cell Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphoproliferative Disorders MYD88 Gene Mutation Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University College London Hospitals, London, United Kingdom

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Phase 1a Only:
  • Histologically confirmed diagnosis of B-cell NHL according to the 2016 World Health Organization (WHO) classification. Diffuse large B-cell lymphoma (DLBCL) includes: DLBCL not otherwise specified (NOS) with or without MYC and BCL2 and/or BCL6 rearrangements; Epstein-Barr virus (EBV) positive DLBCL, NOS; human herpesvirus 8 (HHV8) positive DLBCL, NOS; DLBCL associated with chronic inflammation; and Primary cutaneous DLBCL, leg type. Patients with indolent lymphoma are eligible if they meet criteria for systemic treatment.
  • Clinicopathological diagnosis of Waldenström's Macroglobulinemia (WM) based on the consensus panel criteria from the Second International Workshop on WM
  • Histologically/cytologically confirmed relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL) by cerebrospinal fluid (CSF) or biopsy. PCNSL patients are considered eligible if the Investigator believes that there is no other reasonable treatment alternative.
  • Note: Patients with HIV-associated PCNSL are not eligible.
  • Note: Patients with secondary CNS metastases are eligible assuming they meet other study criteria. Patients with secondary CNS metastases include those who have synchronous systemic and CNS involvement or those who have been previously treated and relapsed with isolated CNS involvement.
  • Phase 1b Only: Histologically confirmed diagnosis of DLBCL according to the 2016 WHO classification including: DLBCL not otherwise specified (NOS) with or without MYC and BCL2 and/or BCL6 rearrangements; Epstein-Barr virus (EBV) positive DLBCL, NOS; HHV8+ DLBCL, NOS; DLBCL associated with chronic inflammation; and Primary cutaneous DLBCL, leg type.
  • Disease relapsed and/or refractory to at least 2 accepted standard systemic regimens for all indications except PCNSL. For PCNSL, patients must be relapsed and/or refractory to at least 1 prior regimen.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening.
  • Adequate organ and bone marrow function, in the absence of growth factors
  • Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol

Exclusion criteria

  • Infection with hepatitis B (HBV), hepatitis C (HCV), or active viral infection with human immunodeficiency virus (HIV).
  • Radiation treatment within 4 weeks prior to first dose of study drug, unless the tumor site continues to increase in size after the patient has completed radiotherapy treatment.
  • Major surgery requiring general anesthesia within 4 weeks prior to first dose of study drug, unless the tumor site continues to increase in size after the patient has completed radiotherapy treatment.
  • Ongoing unstable cardiovascular function including history of myocardial infarction within 3 months of planned start of study drug.
  • Patient has not recovered from any clinically significant AEs of previous treatments to pre-treatment baseline or Grade 1 prior to first dose of study drug.

Treatment and study plan

KT-413

Drug

KT-413 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined dose level.

Primary outcomes

  1. To establish the Maximum Tolerated Dose (MTD)

    Time frame: Within first 3 weeks of treatment

    Phase 1a

  2. Number of Participants with protocol specified Dose Limiting Toxicities (DLTs)

    Time frame: Within first 3 weeks of treatment

    Phase 1a

  3. Dose recommended for future studies

    Time frame: Within first 3 weeks of treatment

    Phase 1a/1b

  4. Clinical Laboratory Abnormalities

    Time frame: Clinical laboratory abnormalities will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy

    Incidence and severity of clinical laboratory abnormalities in serum chemistry, hematology, coagulation parameters, and urinalysis tests as assessed by CTCAE v5.0 (Phase 1a/1b)

  5. Adverse Event Parameters

    Time frame: Adverse Event Parameters will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy

    Incidence and severity of adverse events as assessed by CTCAE v5.0 (Phase 1a/1b)

  6. ECG Parameters

    Time frame: ECG Parameters will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy

    Changes in the ECG parameters, including heart rate and measures PR, QRS, QT, and QTc intervals as assessed by CTCAE v5.0 Phase 1a/1b

Secondary outcomes

  1. Area under the plasma concentration versus time curve for KT-413 from time zero to last quantifiable time point (AUC0-t)

    Time frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)

    Phase 1a/1b

  2. Maximum Plasma Concentration of KT-413 (Cmax)

    Time frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)

    Phase 1a/1b

  3. Time of maximum plasma concentration of KT-413 (Tmax)

    Time frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)

    Phase 1a/1b

  4. Half-life of KT-413 [if data permits (T1/2)]

    Time frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)

    Phase 1a/1b

  5. Amount of KT-413 excreted in urine from time zero to last collected timepoint (Ae0-t)

    Time frame: Urine samples for PK analysis collected during the first cycle (21 day cycle)

    Phase 1a/1b

  6. Evidence of clinical activity of KT-413 as determined by Objective Response Rate (ORR)

    Time frame: From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months

    Phase 1a/1b

  7. Duration of Response (DOR) as assessed by the Investigator

    Time frame: From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months

    Phase 1a/1b

  8. Progression-free survival (PFS) as assessed by the Investigator

    Time frame: From time of entry on study through progression, up to 18 months

    Phase 1b

  9. Disease Control Rate (DCR) as assessed by the investigator

    Time frame: From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months

    Phase 1b

  10. Overall Survival (OS) as assessed by the investigator

    Time frame: From time of entry on study through death or date last known alive at end of follow-up, up to 18 months

    Phase 1b

Other outcomes

  1. KT-413 levels in peripheral blood mononuclear cells

    Time frame: Blood samples for PD analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)

    Phase 1a/1b

Sponsors and collaborators

Lead sponsor

Kymera Therapeutics, Inc.

Industry

Registry information

Official study title

A Phase 1, Multicenter, Open-Label, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, PK/PD, and Clinical Activity of Intravenously Administered KT-413 in Adult Patients with Relapsed or Refractory B-cell NHL

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Feb 10, 2022
Registry last updated
Dec 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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